Hormonal therapy, the major form of treatment for men with metastatic carcinoma of the prostate, produces objective evidence of remission in approximately 60% of patients. If a test were available for predicting response to hormonal therapy, the feminizing side effects of castration and estrogen treatment could be avoided in 40% of such patients and a more effective modality for their treatment could be selected earlier. Based on observations in other endocrine responsive neoplasms, which have demonstrated a correlation between hormonal responsiveness and the presence of specific cytoplasmic receptor proteins, this application proposes to investigate the relationship between androgen receptor concentration and response to hormonal therapy in men with carcinoma of the prostate. The first aim of this proposal is the establishment of a reliable assay for further characterization of the receptor in human prostate. For this purpose, binding to the receptor must be distinguished from binding to testosterone-estradiol binding globulin, a serum protein that also binds with high affinity to dihydrotestosterone. Next, a microassay will be designed to facilitate the use of prostatic tissue obtained by needle biopsy. Using these assays, the kinetics distribution and variation in receptor content in prostatic carcinomas will be investigated and the response to hormonal therapy in men with metastatic disease will be correlated with the content of androgen receptor. Hopefully, this study may provide an important method for predicting the biological behavior of prostatic carcinoma. BIBLIOGRAPHIC REFERENCE: Walsh, P.C., Siiteri, P.K.: Suppression of plasma androgens by spironolactone in castrated men with carcinoma of the prostate. J. Urol. 114:254, 1975.